Synthesis of Lactams via a Chiral Phosphoric Acid-Catalyzed Aniline Cyclization

The enantioenriched
lactams disclosed in this work are synthesized
concisely in four steps. In the penultimate reaction, a benzylamine
species complexes with a chiral phosphoric acid to produce benzo-fused
δ-lactams equipped with an all-carbon quaternary stereocenter.
Partial and full reductions were carried out on the ester and amide
moieties, and a Suzuki–Miyaura cross-coupling expanded the
molecule from the aromatic ring. Finally, our method was successful
at a >1 g scale, indicating that the method has important practical
use.